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Biomedical subjects

M Lishner

Publications and source records attributed to M Lishner.

At least 91 records · Page 5Linked to original sources

In situ hybridization: a simple and sensitive method for detection of trisomy 12 in chronic lymphocytic leukemia.

Chromosome aberrations are detected in only 50% of patients with chronic lymphocytic leukemia (CLL), owing usually to the low mitotic rate exhibited by the neoplastic lymphocytes. Fluorescence in situ hybridization (FISH) is a simple method for identifying numerical abnormalities of the target chromosome in interphase nuclei. Therefore, we used the FISH procedure with chromosome 12-specific a-satellite probe to evaluate 19 patients with CLL. Trisomy 12 was detected in interphase cells of 12 patients (63%). Cytogenetic analysis, performed in nine patients, yielded trisomy 12 in four (44%). FISH detected three patients with trisomy 12 in whom conventional cytogenetic method yielded a normal karyotype. FISH is a simple, reliable, and sensitive method for detection of trisomy 12 in patients with CLL.

Aged↗

Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients.

OBJECTIVE: To evaluate the long-term effect of angiotensin-converting enzyme inhibition on proteinuria and on the rate of decline in kidney function in patients with type II diabetes mellitus and microalbuminuria. DESIGN: Randomized, double-blind, placebo-controlled trial. Each patient was followed for 5 years. SETTING: Six clinics for diabetes mellitus coordinated by a department of medicine in a university hospital in Israel. PATIENTS: Ninety-four normotensive, type II diabetic patients with microalbuminuria and normal renal function. INTERVENTION: The patients were randomly assigned to receive enalapril, 10 mg per day, or placebo. Any increase in blood pressure was treated with long-acting nifedipine. MEASUREMENTS: Albuminuria, blood pressure, serum creatinine, fasting blood glucose, and glycosylated hemoglobin levels, every 3 to 4 months. RESULTS: In the patients treated with enalapril, albuminuria decreased from 143 +/- 64 (mean +/- SD) mg/24 h to 122 +/- 67 mg/24 h during the first year. Thereafter, we observed a slow increase to 140 +/- 134 mg/24 h after 5 years. In the placebo group, albuminuria increased from 123 +/- 58 mg/24 h to 310 +/- 167 mg/24 h after 5 years. (Difference in rate of change in proteinuria [P < 0.05]). Kidney function (expressed as mean reciprocal creatinine) declined by 13% in the placebo group and remained stable (-1%) in the enalapril group (P < 0.05). Control of blood glucose levels remained stable, in both groups, throughout the study. The mean blood pressure was stable in the enalapril group (initial group mean, 99 +/- 2.1 mm Hg; fifth-year mean, 100 +/- 3.2 mm Hg) and increased in the placebo group from an initial mean value of 97 +/- 3.2 mm Hg to 102 +/- 3.4 mm Hg at the end of the study period (P = 0.082). CONCLUSIONS: In normotensive patients with diabetes mellitus type II, the institution of angiotensin-converting enzyme inhibition during early stages of diabetic nephropathy results in long-term stabilization of plasma creatinine levels and of the degree of urinary loss of albumin. These effects are probably independent of the antihypertensive action of these agents.

Adult↗

Teratogenicity and carcinogenicity in a twin exposed in utero to cyclophosphamide.

A 29-year-old pregnant woman diagnosed with acute lymphocytic leukemia maintained remission with daily cyclophosphamide and intermittent prednisone treatment. She delivered a male twin with multiple congenital abnormalities who was diagnosed with papillary thyroid cancer at 11 years of age and stage III neuroblastoma at 14 years of age. The female twin was unaffected and has exhibited normal development to date. First trimester exposure to cyclophosphamide has been associated with major malformations. Metabolites of cyclophosphamide have been demonstrated to be teratogens and carcinogens in animals. Differences in placental or fetal hepatic cytochrome P-450 may account for the variability in response between the twins. In addition, disparity between the twins may be the result of differences in metabolite inactivating enzymes present either in fetal liver or placenta. The risk of second malignancies caused by alkylating agents such as cyclophosphamide has been well documented in adults and children but to the best of our knowledge this is the first description of transplacental second cancer.

Abnormalities, Drug-Induced↗

Clinical detection of BCR-abl fusion by in situ hybridization in chronic myelogenous leukemia.

We describe the use of the fluorescence in situ hybridization (FISH) technique to detect residual Philadelphia chromosome-positive (Ph+) cells in a patient with blastic phase chronic myelogenous leukemia (CML) after aggressive cytoreductive treatment. The analysis was made in interphase nuclei because of the very small number of recognizable metaphases in leukemic patients. FISH was a reliable tool for the detection of chromosome translocations in interphase nuclei as compared with conventional cytogenetic and polymerase chain reaction (PCR) techniques.

Adult↗

Haemorrhagic bullae induced by oral anticoagulants.

A 77-year-old patient developed haemorrhagic bullae on her fingers 30 months after initiation of anti-coagulation treatment with warfarin sodium for chronic atrial fibrillation and mitral insufficiency. The bullae resolved 10 days after discontinuation of the medication. Two weeks after initiation of sintrom, (3-alpha-(4-nitrophenyl)-beta-acetylethyl-4-hydroxy coumarin), the lesions recurred and resolved again upon cessation of the drug. This adverse skin reaction has not been hitherto reported.

Acenocoumarol↗

Fluorescent in situ hybridization for the detection of t(8:14) in Burkitt's lymphoma.

Burkitt's lymphoma cells exhibit the reciprocal balanced chromosomal translocation t(8:14) in 75% of patients. Cytogenetic analysis is time-consuming, requires in vitro culture with mitogens and enables to analyse a relatively small number of cells. We evaluated the role of multicolor fluorescent in situ hybridization (FISH) in the rapid detection of t(8:14) in Burkitt's lymphoma cells. FISH detected the JH/myc translocation in 100% of the cells of five cell lines carrying the classical t(8:14) and in fresh cells obtained from a newly diagnosed Burkitt's lymphoma patient. In contrast, the translocation was not detected in the Bajb cell line that does not carry t(8:14). We conclude that FISH is a rapid and reliable diagnostic tool for the detection of the JH/myc translocation in Burkitt's lymphoma patients.

Biopsy, Needle↗

A comparative analysis of alkylating agent and epipodophyllotoxin-related leukemias.

This review deals with the differences between leukemias--induced by alkylating agents as opposed to a "new form" of treatment related leukemia due to prior exposure to epipodophyllotoxins the latter having a short treatment--disease onset interval, absence of a MDS phase, a monocytic component and cytogenetic abnormalities involving the 11q23 band. The link between the existence of oncogenes or tumor suppressor genes located on the involved portion of chromosome 11 and the development of epipodophyllotoxin-related leukemia still needs to be examined. Alkylating agents--induced leukemias have a longer treatment--disease onset interval, have a prior myelodysplastic syndrome, and are most frequent myeloblastic or myelomonocytic in nature. Karyotype analysis reveals partial or complete deletion of chromosomes no. 5 or 7. This form of leukemia is highly resistant to treatment in the majority of cases. Some of the possible molecular mechanisms of leukemogenesis are discussed.

Alkylating Agents↗

Second malignancies following treatment in non-Hodgkin's lymphoma.

Second malignancies represent an important iatrogenic complication of the treatment of hematologic and other neoplasms. In this review we summarize the literature relating specifically to malignancies developing in the wake of treated non-Hodgkin's lymphoma (NHL). In these patients, the risk of myelodysplastic syndrome (MDS) and acute non lymphocytic leukemia (ANLL) is reported to be increased 10-105 fold over that of the general population. Factors in the development of MDS and ANLL include basic defects in cellular immunity in NHL patients as well as treatment with alkylating agents and low dose total body irradiation. Biologically these secondary MDS and ANLLs are characterized by specific cytogenetic abnormalities and results of treatment are poor. Currently bone marrow transplantation offers the only potential cure. There is no clear statistical evidence that solid tumors occur more frequently after NHL. However, bladder carcinoma, in cyclophosphamide treated patients, and lung cancer have been reported by some to occur with an increased incidence. Further investigation of the molecular events leading to the occurrence of second malignancies in NHL patients and the role played by oncogenes and tumor suppressor genes in this process is still needed.

Actuarial Analysis↗

Maternal and fetal outcome after breast cancer in pregnancy.

We compared 118 women with breast cancer (119 pregnancies) with 269 nonpregnant control subjects matched on important prognostic factors. The distribution of breast cancer stages among the 118 pregnant women was compared with that among 5115 cases of breast cancer in women of reproductive age. Fetal outcome was compared with that of a control group matched for maternal age. Women having breast cancer in pregnancy were 2.5 times more likely to have metastatic disease (95% confidence interval 1.1 to 5.3) and had a significantly lower chance of having stage I disease (p = 0.015). Survival of pregnant women did not differ from that of the controls. Birth weights of babies born to women with breast cancer were significantly lower than those of control babies after gestational age was adjusted for (3010 +/- 787 vs 3451 +/- 515 gm, p = 0.016). The two stillbirths in 85 pregnancies that continued to term (2.4%) was not statistically different from the 1.1% rate for Ontario. We analyzed all 223 births occurring in women who had any form of cancer in the same hospital during the same 30 years. There were 10 stillbirths among these 223 cases (4.4%), significantly more than expected in Ontario (p less than 0.0005; relative risk of 4.23 with 95% confidence interval 2.0 to 7.8). Our data suggest that pregnant women are at a higher risk of presenting with advanced disease because pregnancy impedes early cancer detection.

Abortion, Spontaneous↗

Case report: unusual presentation of splenic hamartoma; computed tomography and ultrasonic findings.

Hamartomas of the spleen are rare benign tumours, which are usually asymptomatic, incidental findings at laparotomy or autopsy (Komakl and Gombas, 1976; Brinkley and Lee, 1981; Norowitz and Morehouse, 1989). There are a few well documented reports of symptomatic splenic hamartoma associated with haematological disturbances, marked splenomegaly or even spontaneous rupture that required an emergency operation (Iozzo et al., 1980; Morgenstern et al., 1984). We report a patient with splenic hamartoma who presented with splenomegaly and iron deficiency anaemia. Computed tomographic (CT) and ultrasound (US) evaluation demonstrated an inhomogeneous mass within the enlarged spleen. Malignant melanoma was mistakenly diagnosed by US-guided fine needle aspiration of the mass, and necessitated splenectomy. The final diagnosis was hamartoma of the spleen.

Diagnosis, Differential↗

Maternal and foetal outcome following Hodgkin's disease in pregnancy.

The peak incidence of Hodgkin's disease occurs during the reproductive age, and its association with pregnancy is at a rate of between 1:1,000-1:6,000. We studied the effects of Hodgkin's Disease on the course and survival of 48 women who had Hodgkin's Disease and who were pregnant, and compared their outcome with non-pregnant matched women who were of similar stage of disease, age at diagnosis, and calenderic year of treatment. Twenty-year survival of pregnant women with Hodgkin's Disease was not different from that of their matched controls. Pregnant women with Hodgkin's Disease had similar distribution of stages to the controls.

Adult↗

Late doxorubicin cardiotoxicity.

The occurrence of late congestive heart failure (CHF) as the first clinical manifestation of doxorubicin-induced cardiac toxicity is unusual in children and very rare in adults. However, subclinical cardiac dysfunction is commonly detected in children years after treatment with doxorubicin containing regimens. We report a 58 year old woman who developed stage IV CHF 7 years after completion of doxorubicin treatment for carcinoma of the ovary. Occult cardiac dysfunction was first demonstrated by radionuclide angiography 6 years prior to the occurrence of the clinical manifestations. This unique course of the disease and the management of the CHF are discussed.

Coronary Angiography↗

Colchicine analogues: effect on amyloidogenesis in a murine model and, in vitro, on polymorphonuclear leukocytes.

Colchicine has been used in diverse clinical settings such as gout, familial Mediterranean fever, liver cirrhosis, Behcet's disease and pericarditis. It also has an antimitotic potential hitherto unexplored due to its narrow therapeutic toxic ratio. The aim of the present study was to compare the effectiveness and the toxicity of colchicine and three analogues: thiocolchicine, 2,3 dimethyl-colchicine and 3-dimethylthiocolchicine in the blockage of amyloid synthesis in a murine model. 3-demethylthiocolchicine was equipotent to colchicine in the blockage of casein induced amyloidogenesis. However, it was markedly less toxic (LD50 11.3 mg kg-1 vs. 1.6 mg kg-1). Thiocolchicine was toxic (LD50 1.0 mg kg-1) and 2,3 didemethyl-colchicine was far less effective. The effect of 3-dimethylthiocolchicine on polymorphonuclear leukocytes was then compared to colchicine. The effect of this analogue on inhibition of chemotaxis was equivalent to that of colchicine whereas the latter was superior to the analogue in the suppression of phagocytosis (by a ratio of 2:1) and in the inhibition of bactericidal activity (by a ratio of 10:1). Since in therapeutic concentrations the only detectable effect of colchicine on PMNs is inhibition of chemotaxis, our data may point to 3-demethylthiocolchicine as an optional, perhaps superior alternative to colchicine for some of its therapeutic indications.

Amyloid↗

The effects of impaired liver function on the elimination of antineoplastic agents.

OBJECTIVE: To critically review available data on the disposition of cancer chemotherapy in patients with hepatic dysfunction, and to derive at dose recommendation. DATA SOURCES: All published studies in English. STUDY SELECTION: Both human and animal studies. DATA SYNTHESIS: The available studies were sequentially qualitatively described and critically discussed. CONCLUSIONS: The liver is responsible for the metabolism and elimination of many anticancer agents. Their accumulation during hepatic insufficiency may expose the patient to increased risk of drug toxicity. A variety of clinical methods have been described to estimate the need to decrease doxorubicin dose according to degree of hepatic failure to avoid serious toxicity. In some studies prospective ascertainment of clinical indices such as hepatic enzymes and bilirubin was successful in preventing doxorubicin-induced hepatotoxicity. Liver dysfunction has a major impact on cyclophosphamide pharmacokinetics. However, because such impairment leads to less production of the active aldophosphamide, fewer adverse effects were observed in hepatically impaired patients. Vinca alkaloids are extensively metabolized by the liver and excreted in the bile. Systemic exposure to these drugs is inversely correlated to the degree of hepatic failure measured by serum alkaline phosphatase. Although hepatic metabolism is a major route of elimination of fluorouracil, the kidney also plays an important role in its elimination. It has been suggested to reduce its dose in cirrhotic patients. Available pharmacokinetic data and their clinical implications are also discussed for azathioprine, mercaptopurine, etoposide, epirubicin, amsacrine, cytarabine, and other less-studied drugs. Recommendations for dose adjustments are presented and discussed.

Animals↗

Second primary malignancies following diagnosis of small-cell lung cancer.

PURPOSE AND METHODS: The records of 800 patients with small-cell carcinoma of the lung (SCLC) treated between 1971 and 1985 at University of Toronto-affiliated hospitals were reviewed for the occurrence and relative risk of second primary malignancies (SPMs). Almost all patients who developed a SPM were treated previously with chemotherapy and radiation therapy. RESULTS: Nineteen metachronous SPMs (MSPMs) and 11 synchronous SPMs (SSPMs) were identified. SSPMs were detected between 1 and 12 months after the diagnosis of SCLC. The MSPMs were identified between 1 and 10 years after the diagnosis of SCLC. MSPMs included non-small-cell lung cancer (NSCLC) (four patients), hematologic malignancies (HM) (three patients), and 12 with other solid tumors (OST). The median survival times after the diagnosis of MSPM was 33 months, 10 months, and 1 month, respectively, for those with NSCLC, OST, and HM. Expected cancer incidence rates were used to compute a relative risk rate for developing a MSPM in a subset of 392 patients on whom accurate follow-up information was available. The calculated relative risk for all tumors was 3.73. The relative risk for the development of secondary NSCLC was 6.83. CONCLUSION: We suggest that increased predisposition to SPM may relate to secondary effects of multimodality treatment and biologic considerations.

Aged↗

Systemic lupus erythematosus and chronic lymphocytic leukemia: rare coexistence in three patients, with comments on pathogenesis.

We describe three patients with coexistent chronic lymphatic leukemia (CLL) and systemic lupus erythematosus (SLE). In two patients, the CLL was present before or coexistent with the SLE when the SLE was diagnosed, while in the third, the CLL developed 5 years after the diagnosis of SLE was first made. Although the association of autoimmune diseases and lymphoproliferative disorders is well established, only a few patients with coexistent CLL and concomitant SLE have been reported. The possible pathogenesis of this rare association is discussed.

Adult↗

A new liver and soft tissue biopsy instrument.

A new liver biopsy instrument taking the form of a suction biopsy syringe with two pistons and a Menghini needle, is described. A vacuum is first created, and the whole procedure is effected by a continuous uninterrupted movement into the liver and instantaneous withdrawal. The syringe is held in one hand. The procedure is very simple and requires minimal training. A total of 118 biopsies have been performed. The specimens were suitable for histopathological examination. Pain was minimal and there were no complications.

Biopsy, Needle↗